ABSTRACT Alzheimer's disease (AD) is a common form of dementia, but little data exist on the risk and prevalence of AD among American Indians and Alaska Natives (AI/ANs). Precision medicine (PM) has potential for detecting and treating diseases such as AD. PM combines data on clinical, genomic, biomarker, and environmental factors with data on health behaviors to assess individual risk of a given disease. It can maximize the effectiveness of tailored clinical management. However, no research has addressed AI/AN preferences for communicating educational or recruitment information for AD or PM studies. AI/ANs experience communication barriers to research participation, as well as prefer visual aids that assist comprehension and communication that align with Native traditions. In 2015, President Obama announced a $215 million PM initiative which emphasizes adequate representation of racial and ethnic minorities. In 2016, NIH funded 8 healthcare organizations to assemble a cohort of 1 million people who will contribute blood and urine samples along with health, environmental, and lifestyle data to a population-based repository for PM research (the All of Us Research Program). We will collaborate with one grantee ? the University of Arizona/Banner Health ? that will enroll 10,000 AI/ANs -- to evaluate methods to recruit AI/ANs at their Phoenix-Tucson clinical facilities. AI/AN informants will help create culturally appropriate recruitment materials (brochures, digital stories) for AD and PM research. Finally, we will conduct a pragmatic randomized controlled trial with 4,000 AI/ANs enrollees in the All of Us cohort. Participants will receive either a standard educational brochure on AD and PM and the importance of research (control) or a culturally tailored, graphics-rich brochure with identical information, and view a digital story featuring personal narratives of AI/ANs on AD (intervention). Participants will then be invited to complete an optional AD-PM Module to assesses AD knowledge and attitudes, health literacy, ethnic identify, and cognition. Upon completion, they will join other AI/ANs who are interested in future AD and PM research, and link their All of Us data and biospecimens to their AD-PM Module data. Our 2 primary outcomes will be completion of the AD-PM Module and enrollment in the AD-PM Cohort. The Specific Aims are to: 1) to evaluate recruitment strategies for AI/ANs in the UAZB program, and address factors that might affect implementation of our trial; 2) create culturally tailored materials on AD and PM, and evaluate their clarity and acceptability; 3) conduct a randomized controlled trial to test the effect of these materials on completion of the AD-PM Module and enrollment in the AD-PM Cohort; and 4) identify patient-level predictors of AD-PM Cohort enrollment, and evaluate potential differences in the effectiveness of recruitment approach by age, sex, education, cultural identity, and rurality. The AD-PM Cohort will represent a unique resource for alleviating the stark underrepresentation of AI/ANs in AD and PM research. Results will highlight communication strategies that facilitate or hinder AI/AN recruitment, elucidate knowledge gaps regarding AD and PM.